Depression in children

McConnell R, Pacheco F, Wahlberg K, et al. 1999. Subclinical health effects of environmental pesticide contamination in a developing country Cholinesterase depression in children. Environ Res A81 87-91. 

Merry S, McDowell H, Hetrick S, Bir J, Muller N. Psychological and/or educational interventions for the prevention of depression in children and adolescents. Cochrane Database Syst Rev 2004. 

Ryan, N., and Dahl, R. (1993) The biology of depression in children and adolescents. In Mann, J. and Kupfer, D., eds. The Biology of Depressive Disorders. New York Plenum Press, pp. 37-58. 

If at the end of the continuation phase it is decided that the antidepressants should be discontinued, this should be done gradually (e.g., over 6 weeks) to avoid withdrawal effects such as sleep disturbance, irritability, or gastrointestinal symptoms, which may lead the clinician to misinterpret the need for continued medication treatment. Clinical practice has suggested that rapid discontinuation of antidepressants may precipitate a relapse or recurrence of depression. In children and adolescents, it is recommended that treatment be discontinued while they are on extended vacations, rather than during the school year. 

Emslie, G.J., Heiligenstein, J.H., Hoog, S.L., Judge, R., Brown E.B., and Nilsson, M. (2000) Fluoxetine for acute treatment of depression in children and adolescents a placebo controlled randomized clinical trial. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico. 

Finch, A.J., Lipovsky, J.A., and Casat, C.D. (1989) Anxiety and depression in children and adolescents negative affectivity or separate constructs In Kendall, P.C. and Watson, D. eds. Anxiety and Depression Distinctive and Overlapping Features. San Diego Academic Press, pp. 171-196. 

D. (1985) But are they cases Validity of DSM-III major depression in children identified in a family study. Am J Psychiatry 142 687-691. 

Ryan ND, Dahl RE The biology of depression in children and adolescents, in Biology of Depressive Disorders, Part B Subtypes of Depression and Gomorbid Disorders. Edited by Mann JJ, Kupfer D. New York, Plenum, 1994 Rybakowski J, Erazer A, Mendels J Lithium efflux from erythrocytes incubated in vitro during lithium carbonate administration. Communications in Psychopharmacology 2 105-112, 1978... 

Thus, the upper limit to the therapeutic range is a function of toxicity rather than reduced efficacy in contrast to the other TCAs. Perry et al. ( 326) proposed a minimal threshold for this tertiary amine TCA of 265 ng/mL (imipramine plus desimipramine) with a remission rate of 42% above this threshold versus 15% below it. Of note, this threshold for optimal antidepressant response is closer to the threshold for CNS and cardiac toxicity than for any other TCA. Preskorn and colleagues ( 327) found a lower optimal threshold for imipramine plus desimipramine (125 ng/mL) when it was used to treat clinical depression in children and adolescents than when used in adults. 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

From 1996 to 1997, 792,000 prescriptions for SSRIs were written to treat depression in children and adolescents between 6 and 18 years of age, primarily because of the safety of these medications compared with TCAs and because of growing evidence of their efficacy (116, 117). 

Preskorn SH, Weller E, Weller R. Depression in children relationship between plasma imipramine levels and response. J Clin Psychiatry 1982 43 450-453. 

Preskorn SH, Weller E, Jerkovich G, et al. Depression in children concentration-dependent CNS toxicity of tricyclic antidepressants. Psychopharmacol Bull 1988 24 140-142. 

Besides biasing the results, companies have also suppressed unfavorable research. GlaxoSmithKline did not publish results that showed that paroxetine (Paxil ) was ineffective for the treatment of depression in children and adolescents because, according to an internal company memo, "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine" (Kondro and Sibbald 2004 783). The Wall Street foumal claims that "internal Merck e-mails and marketing materials as well as interviews with outside scientists show that the company fought forcefully for years to keep safety concerns from destroying the drug s [Vioxx s] commercial prospects" (Mathews and Martinez 2004 Al). 

Children. Despite classical psychoanalytic notions suggesting that children do not become depressed, recent evidence is quite to the contrary. Unfortunately, very little controlled research has been done on the use of antidepressants to treat depression in children, so no antidepressant is currently approved for treatment of depression in children. However, many of the newer antidepressants have been extensively tested in children with other conditions. For example, some antidepressants are approved... 

Regarding the drug treatment of depression in children, there is so far a paucity of good clinical trials to show that antidepressants are effective. Several small studies suggest that daily doses of up to 5mg/kg of imipramine may be beneficial, but there is no data to show whether other types of antidepressant medication are effective. The side effects and toxicity of tricyclic antidepressants are legion and have been discussed in detail elsewhere. Undoubtedly the SSRIs should now be the drugs of first choice in the treatment of depression in children. 

Varni, J. W., Setoguchi, Y., Rappaport, L. T., and Talbot, D. (1991). Effects of stress, social support, and self-esteem on depression in children with limb deficiencies. Arch. Phys. Med. Rehabilitation 72,1053-1058. 

In Great Britain, all SSRI antidepressants, except fluoxetine, have been banned for use in treating depression in children. The main concern surrounded suicidality that was increased with SSRIs in general, including fluoxetine (Committee on Safety of Medicines, 2003). 

The viewpoint of the editorial is so warped that it does not even mention that the FDA also found that the vast majority of clinical trials showed that antidepressants are ineffective in treating depression in children. As already noted, only 3 of 15 placebo-controlled clinical trials showed any efficacy. (Two of the three positive studies were sponsored by Eli Lilly, with Graham Emlsie, a close Lilly collaborator, as the first author see subsequent discussion.) Also remember FDA committee member and epidemiologist Thomas Newman s (2004) observations that the adverse effects of the antidepressants were much better established than their efficacy, which could largely be accounted for by the placebo effect. 

The editorial in the American Journal of Psychiatry is miffed that the FDA warned about antidepressant-induced suicidality without providing another alternative. But the so-called alternatives for treating depression in children—psychosocial and educational interventions—should have already become the only treatments for childhood depression. 

In children, the causes of this despair and loss of hope are almost always apparent in the first consultation session, providing it involves the family and includes an evaluation of the child s school life. In children, depression almost always revolves around problems at school and in the home, everything from bullying at school and abuse at home to academic school failure, painful peer relationships, and family conflicts over how to raise the child. The treatment of depression in children requires, first, finding out how and why the child became depressed and, second, helping the child, the family, the school, and all the other participants in the child s life restore hope in the child. Children have many needs, including a stable family, rational discipline, unconditional love, stimulating educational environments, physical security, and emotional safety. The object of therapy is to identify the unmet needs and to help adults meet them. 

As documented in chapter 6, the scientific literature demonstrates, and the FDA admitted at its 2004 hearings, that there is no substantial evidence supporting the usefulness of antidepressants in treating depression in children. What about the treatment of adults Is it possible that the antidepressants are not antidepressants at all ... 

When a drug fails to get FDA approval for a particular indication, such as GSK s Paxil for the treatment of depression in children, drug companies have exercised their proprietary right not to release information about the testing. In the case of Paxil, the company refused to release its clinical trial data for testing Paxil in children and adolescents, but as documented earlier in this chapter, it nonetheless used its influence with the journals and its sales force to spread the lie that the drug was safe and effective for children. 

Great Britain went on to ban all of the SSRIs for use in depression in children except for Prozac, mistakenly giving credence to two clinical trials of Prozac conduced by Graham Emsley, a close associate of Eli Lilly (chapter 6). 

Office of New York State Attorney General Eliot Spitzer. (2004, June 2). Major pharmaceutical firm concealed drug information GlaxoSmithKline mislead doctors about the safety of drug used to treat depression in children. Retrieved from http //www. badfaithinsurance.org... 

A previous report that rectal and intravenous diazepam can cause respiratory depression in children with seizures (SEDA-24, 84) has been challenged (64,65). The authors of the second comment stated that this complication does not occur when rectal diazepam gel is used without other benzodiazepines they also recommended that during long-term therapy families should be instructed not to give rectal diazepam more than once every 5 days or five times in 1 month. 

Kriel RL, Cloyd JC, Pellock JM. Respiratory depression in children receiving diazepam for acute seizures a prospective study. Dev Med Child Neurol 2000 42(6) 429-30. 

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